| 主权项 |
1. A method of determining the presence or absence, in a urine sample from a patient, of bladder or prostate cancer cells which over-express NQO1 and/or NQO2, the method comprising:
i. contacting the urine sample, or a processed derivative thereof, with a compound of general formula (I), (Ia), (Ib), (Ic), (Id), (Ie) or (If) or a salt of any thereof where applicable, wherein the urine sample contains or is suspected of containing bladder or prostate cancer cells which over-express NQO1 and/or NQO2; ii. optionally, in the case where the bladder or prostate cancer cells over-express or are suspected of over-expressing NQO2, adding an NQO2 co-substrate to the sample; and iii. determining the presence or absence of a compound of the formula:
z-XH; or an ion of the formula:
z-X−; wherein z and X are as defined in general formula (I), wherein presence of the compound or ion indicates the presence in the sample of cancer cells which over-express NQO1 and/or NQO2 wherein general formula (I) is: wherein R1, R2, R3, R4 and R5 each independently represent hydrogen, halogen, NR6R7, C(O)NR6R7 or C1-C6 alkyl, —O(C1-C6 alkyl) or C(O)O(C1-C6 alkyl), any of which may optionally be substituted with one or more reactive substituents; R6 and R7 each independently represent hydrogen or C1-C6 alkyl optionally substituted with halo; or R1 and R2 together with the carbon atoms to which they are attached form a 5- or 6-membered optionally substituted aromatic, heteroaromatic, carbocyclic or heterocyclic ring system; X is O, S or NR8;
R8 is hydrogen, or C1-C3 alkyl; Y is O, S or NR9;
R9 is hydrogen, or C1-C3 alkyl; z is a moiety which is covalently linked to the remainder of the molecule and which, on reduction of the compound of general formula (I), is cleaved from the remainder of the molecule to form a detectable compound z-XH or ion z-X−; general formula (Ia) is: wherein R1, R2, R3, R4 and R5 each independently represent hydrogen, halogen, NR6R7, C(O)NR6R7 or C1-C6 alkyl, —O(C1-C6 alkyl) or C(O)O(C1-C6 alkyl), any of which may optionally be substituted with one or more reactive substituents; R6 and R7 each independently represent hydrogen or C1-C6 alkyl optionally substituted with halo; or R1 and R2 together with the carbon atoms to which they are attached form a 5- or 6-membered optionally substituted aromatic, heteroaromatic, carbocyclic or heterocyclic ring system; R1′, R2′, R3′, R4′ and R5′ each independently represent hydrogen, halogen, NR6R7, C(O)NR6R7 or C1-C6 alkyl, —O(C1-C6 alkyl) or C(O)O(C1-C6 alkyl), any of which may optionally be substituted with one or more reactive substituents; R6 and R7 each independently represent hydrogen or C1-C6 alkyl optionally substituted with halo; or R1′ and R2′ together with the carbon atoms to which they are attached form a 5- or 6-membered optionally substituted aromatic, heteroaromatic, carbocyclic or heterocyclic ring system; X is O, S or NR8;
R8 is hydrogen, or C1-C3 alkyl; Y is O, S or NR9;
R9 is hydrogen, or C1-C3 alkyl; X′ is O, S or NR8;
R8 is hydrogen, or C1-C3 alkyl; Y′ is O, S or NR9;
R9 is hydrogen, or C1-C3 alkyl; z is a moiety which is covalently linked to the remainder of the molecule and which, on reduction of the compound of general formula (I), is cleaved from the remainder of the molecule to form a detectable compound z-XH or ion z-X−; general formula (Ib) is: wherein R1, R2 and R4 each independently represent hydrogen, halogen, NR6R7, C(O)NR6R7 or C1-C6 alkyl, —O(C1-C6 alkyl) or C(O)O(C1-C6 alkyl), any of which may optionally be substituted with one or more reactive substituents; R6 and R7 each independently represent hydrogen or C1-C6 alkyl optionally substituted with halo; or R1 and R2 together with the carbon atoms to which they are attached form a 5- or 6-membered optionally substituted aromatic, heteroaromatic, carbocyclic or heterocyclic ring system; Rx is H, or C1-C3 alkyl X is O, S or NR8;
R8 is hydrogen, or C1-C3 alkyl; z is a moiety which is covalently linked to the remainder of the molecule and which, on reduction of the compound of general formula (I), is cleaved from the remainder of the molecule to form a detectable compound z-XH or ion z-X−; general formula (lc) is: wherein R4, R5, R10, R11, R12 and R13 each independently represent hydrogen, halogen, NR6R7, C(O)NR6R7 or C1-C6 alkyl, —O(C1-C6 alkyl) or C(O)O(C1-C6 alkyl), any of which may optionally be substituted with one or more reactive substituents; R6 and R7 each independently represent hydrogen or C1-C6 alkyl optionally substituted with halo; X is O, S or NR8;
R8 is hydrogen, or C1-C3 alkyl; Y is O, S or NR9;
R9 is hydrogen, or C1-C3 alkyl; z is a moiety which is covalently linked to the remainder of the molecule and which, on reduction of the compound of general formula (I), is cleaved from the remainder of the molecule to form a detectable compound z-XH or ion z-X−; general formula (Id) is: wherein: X is O, S or NR8;
R8 is hydrogen, or C1-C3 alkyl; R10, R11, R12 and R13 each independently represent hydrogen, halogen, NR6R7, C(O)NR6R7 or C1-C6 alkyl, —O(C1-C6 alkyl) or C(O)O(C1-C6 alkyl), any of which may optionally be substituted with one or more reactive substituents; R6 and R7 each independently represent hydrogen or C1-C6 alkyl optionally substituted with halo; z is a moiety which is covalently linked to the remainder of the molecule and which, on reduction of the compound of general formula (I), is cleaved from the remainder of the molecule to form a detectable compound z-XH or ion z-X−; general formula (Ie) is: wherein R10, R11, R12 and R13 each independently represent hydrogen, halogen, NR6R7, C(O)NR6R7 or C1-C6 alkyl, —O(C1-C6 alkyl) or C(O)O(C1-C6 alkyl), any of which may optionally be substituted with one or more reactive substituents; R6 and R7 each independently represent hydrogen or C1-C6 alkyl optionally substituted with halo; X is O, S or NR8;
R8 is hydrogen, or C1-C3 alkyl; Y is O, S or NR9;
R9 is hydrogen, or C1-C3 alkyl; z is a moiety which is covalently linked to the remainder of the molecule and which, on reduction of the compound of general formula (I), is cleaved from the remainder of the molecule to form a detectable compound z-XH or ion z-X−; general formula (If) is: wherein R10, R11, R12 and R13 each independently represent hydrogen, halogen, NR6R7, C(O)NR6R7 or C1-C6 alkyl, —O(C1-C6 alkyl) or C(O)O(C1-C6 alkyl), any of which may optionally be substituted with one or more reactive substituents; R6 and R7 each independently represent hydrogen or C1-C6 alkyl optionally substituted with halo; R14 is H or C1-C6 alkyl and X is O, S or NR8;
R8 is hydrogen, or C1-C3 alkyl; Y is O, S or NR9;
R9 is hydrogen, or C1-C3 alkyl; z is a moiety which is covalently linked to the remainder of the molecule and which, on reduction of the compound of general formula (I), is cleaved from the remainder of the molecule to form a detectable compound z-XH or ion z-X−. |
